Site-Selective Polyfluoroaryl Modification and Unsymmetric Stapling of Unprotected Peptides.

Peptide stapling is recognized as an effective strategy for improving the proteolytic stability and cell permeability of peptides. In this study, we present a novel approach for the site-selective unsymmetric perfluoroaryl stapling of Ser and Cys residues in unprotected peptides. The stapling reaction proceeds smoothly under very mild conditions, exhibiting a remarkably rapid reaction rate. It can furnish stapled products in both liquid and solid phases, and the presence of nucleophilic groups other than Cys thiol within the peptide does not impede the reaction, resulting in uniformly high yields. Importantly, the chemoselective activation of Ser ß-C(sp3)-H enables the unreacted -OH to serve as a reactive handle for subsequent divergent modification of the staple moiety with various therapeutic functionalities, including a clickable azido group, a polar moiety, a lipid tag, and a fluorescent dye. In our study, we have also developed a visible-light-induced chemoselective C(sp3)-H polyfluoroarylation of the Ser ß-position. This reaction avoids interference with the competitive reaction of Ser -OH, enabling the precise late-stage polyfluoroarylative modification of Ser residues in various unprotected peptides containing other highly reactive amino acid residues. The biological assay suggested that our peptide stapling strategy would potentially enhance the proteolytic stability and cellular permeability of peptides.

A monodispersed metal-complexing peptide-based polymer for mass cytometry enabling spectral applications.

We report the synthesis of a novel class of metal-complexing peptide-based polymers, which we name HyperMAPs (Hyper-loaded MetAl-complexed Polymers). The controlled solid-phase synthesis of HyperMAPs' scaffold peptide provides our polymer with a well-defined molecular structure that allows for an accurate on-design assembly of a wide variety of metals. The peptide-scaffold features a handle for direct conjugation to antibodies or any other biomolecules by means of a thiol-maleimide-click or aldehyde-oxime reaction, a fluorogenic moiety for biomolecule conjugation tracking, and a well-defined number of functional groups for direct incorporation of metal-chelator complexes. Since metal-chelator complexes are prepared in a separate reaction prior to incorporation to the peptide scaffold, polymers can be designed to contain specific ratios of metal isotopes, providing each polymer with a unique CyTOF spectral fingerprint. We demonstrate the complexing of 21 different metals using two different chelators and provide evidence of the application of HyperMAPs on a 13 parameter CyTOF panel and compare its performance to monoisotopic metal-conjugated antibodies.

Sulfhydryl-functionalized 3D MXene-AuNPs enabled electrochemical sensors for the selective determination of Pb2+, Cu2+ and Hg2+ in grain.

Herein, we made 3D MXene-AuNPs by in situ growth of gold nanoparticles (AuNPs) on the surface of MXene by chemical reduction method, and then introduced three sulfhydryl (-SH) compounds as functionalized modifiers attached to the AuNPs to form a highly selective composite material for the detection of Pb2+, Cu2+, and Hg2+, respectively. The doping of AuNPs changes the microstructure of 2D MXene and generates more active sites. On a sensing platform based on ITO array electrodes, the detection system was optimised with sensitivities up to 1.157, 0.846 and 0.799 µA·µg-1Lcm-2 (Pb2+, Cu2+, and Hg2+). The selectivity of MXene@AuNPs was effectively improved by sulfhydryl group modification. In the range of 1-1300 µg L-1, the detection limits of three ions were 0.07, 0.13 and 0.21 µg L-1. In addition, this method can efficiently and accurately detect heavy metal ions in four cereal samples with consistent results with inductively coupled plasma mass spectrometry.

Peptide and Protein Desulfurization with Diboron Reagents.

In this Letter, we report a direct and robust desulfurization method employing water-soluble phosphine, specifically tris(2-carboxyethyl)phosphine hydrochloride (TCEP), and tetrahydroxydiboron (B2(OH)4), which serves as a radical initiator. This innovative reaction exhibits compatibility with a diverse array of substrates, including cysteine residues in chemically synthesized oligopeptides and cyclic peptides, alkyl thiols in bioactive molecules, disulfides in commercial proteins, and selenocysteine. We optimized the reaction conditions to minimize the formation of undesired oxidized and borylated byproducts. Furthermore, the refined desulfurization process is executed after native chemical ligation (NCL) in a single pot, streamlining the existing synthetic approaches. This demonstrates its potential applications in the synthesis of complex peptides and proteins, showcasing a significant advancement in the field.

Evaluation of maternal serum thiol and ischemia-modified albumin levels in cases of placenta previa: A case-control study in a tertiary center.

AIM: We aim to compare the maternal serum thiol and ischemia-modified albumin (IMA) levels between pregnant women with placenta previa and those with uncomplicated pregnancies and to determine whether changes in these levels were useful in predicting cases of abnormally invasive placenta (AIP). METHODS: Fifty-five pregnant women diagnosed with placenta previa according to the diagnostic criteria (case group) were compared to 100 women with uncomplicated pregnancies of similar demographic characteristics (control group). The patients with placenta previa were further divided into two subgroups: AIP (n = 20) and placenta previa without invasion (n = 35). The maternal serum native thiol, total thiol, disulfide, and IMA levels of the groups were evaluated. RESULTS: The native thiol, total thiol, and IMA values were significantly lower in the case group than in the control group (p < 0.001). The disulfide values were similar between the study and control groups (p = 0.488). When the AIP and placenta previa without invasion groups were compared, the levels of native thiol, total thiol, disulfide, and IMA were similar (p > 0.05). CONCLUSIONS: Maternal serum thiol and IMA levels were lower in placenta previa cases compared to the control group. However, these parameters were not useful in predicting AIP cases.

Viscoelastic stiffening of gelatin hydrogels for dynamic culture of pancreatic cancer spheroids.

The tumor microenvironment (TME) in pancreatic adenocarcinoma (PDAC) is a complex milieu of cellular and non-cellular components. Pancreatic cancer cells (PCC) and cancer-associated fibroblasts (CAF) are two major cell types in PDAC TME, whereas the non-cellular components are enriched with extracellular matrices (ECM) that contribute to high stiffness and fast stress-relaxation. Previous studies have suggested that higher matrix rigidity promoted aggressive phenotypes of tumors, including PDAC. However, the effects of dynamic viscoelastic matrix properties on cancer cell fate remain largely unexplored. The focus of this work was to understand the effects of such dynamic matrix properties on PDAC cell behaviors, particularly in the context of PCC/CAF co-culture. To this end, we engineered gelatin-norbornene (GelNB) based hydrogels with a built-in mechanism for simultaneously increasing matrix elastic modulus and viscoelasticity. Two GelNB-based macromers, namely GelNB-hydroxyphenylacetic acid (GelNB-HPA) and GelNB-boronic acid (GelNB-BA), were modularly mixed and crosslinked with 4-arm poly(ethylene glycol)-thiol (PEG4SH) to form elastic hydrogels. Treating the hybrid hydrogels with tyrosinase not only increased the elastic moduli of the gels (due to HPA dimerization) but also concurrently produced 1,2-diols that formed reversible boronic acid-diol bonding with the BA groups on GelNB-BA. We employed patient-derived CAF and a PCC cell line COLO-357 to demonstrate the effect of increasing matrix stiffness and viscoelasticity on CAF and PCC cell fate. Our results indicated that in the stiffened environment, PCC underwent epithelial-mesenchymal transition. In the co-culture PCC and CAF spheroid, CAF enhanced PCC spreading and stimulated collagen 1 production. Through mRNA-sequencing, we further showed that stiffened matrices, regardless of the degree of stress-relaxation, heightened the malignant phenotype of PDAC cells. STATEMENT OF SIGNIFICANCE: The pancreatic cancer microenvironment is a complex milieu composed of various cell types and extracellular matrices. It has been suggested that stiffer matrices could promote aggressive behavior in pancreatic cancer, but the effect of dynamic stiffening and matrix stress-relaxation on cancer cell fate remains largely undefined. This study aimed to explore the impact of dynamic changes in matrix viscoelasticity on pancreatic ductal adenocarcinoma (PDAC) cell behavior by developing a hydrogel system capable of simultaneously increasing stiffness and stress-relaxation on demand. This is achieved by crosslinking two gelatin-based macromers through orthogonal thiol-norbornene photochemistry and post-gelation stiffening with mushroom tyrosinase. The results revealed that higher matrix stiffness, regardless of the degree of stress relaxation, exacerbated the malignant characteristics of PDAC cells.

The crystal structure of mycothiol disulfide reductase (Mtr) provides mechanistic insight into the specific low-molecular-weight thiol reductase activity of Actinobacteria.

Low-molecular-weight (LMW) thiols are involved in many processes in all organisms, playing a protective role against reactive species, heavy metals, toxins and antibiotics. Actinobacteria, such as Mycobacterium tuberculosis, use the LMW thiol mycothiol (MSH) to buffer the intracellular redox environment. The NADPH-dependent FAD-containing oxidoreductase mycothiol disulfide reductase (Mtr) is known to reduce oxidized mycothiol disulfide (MSSM) to MSH, which is crucial to maintain the cellular redox balance. In this work, the first crystal structures of Mtr are presented, expanding the structural knowledge and understanding of LMW thiol reductases. The structural analyses and docking calculations provide insight into the nature of Mtrs, with regard to the binding and reduction of the MSSM substrate, in the context of related oxidoreductases. The putative binding site for MSSM suggests a similar binding to that described for the homologous glutathione reductase and its respective substrate glutathione disulfide, but with distinct structural differences shaped to fit the bulkier MSSM substrate, assigning Mtrs as uniquely functioning reductases. As MSH has been acknowledged as an attractive antitubercular target, the structural findings presented in this work may contribute towards future antituberculosis drug development.

Piperazine-Fused Cyclic Disulfides Unlock High-Performance Bioreductive Probes of Thioredoxins and Bifunctional Reagents for Thiol Redox Biology.

We report piperazine-fused six-membered-cyclic disulfides as redox substrates that unlock best-in-class bioreduction probes for live cell biology, since their self-immolation after reduction is unprecedentedly rapid. We develop scalable, diastereomerically pure, six-step syntheses that access four key cis- and trans-piperazine-fused cyclic dichalcogenides without chromatography. Fluorogenic redox probes using the disulfide piperazines are activated >100-fold faster than the prior art monoamines, allowing us to deconvolute reduction and cyclization rates during activation. The cis- and trans-fused diastereomers have remarkably different reductant specificities, which we trace back to piperazine boat/chair conformation effects: the cis-fused disulfide C-DiThia is activated only by strong vicinal dithiol reductants, but the trans-disulfide T-DiThia is activated even by moderate concentrations of monothiols such as GSH. Thus, in cellular applications, cis-disulfide probes selectively report on the reductive activity of the powerful thioredoxin proteins, while trans-disulfides are rapidly but promiscuously reactive. Finally, we showcase late-stage diversifications of the piperazine-disulfides, promising their broad applicability as redox-cleavable cores for probes and prodrugs that interface powerfully with cellular thiol/disulfide redox biology, for solid phase synthesis and purification, and for stimulus-responsive linkers in bifunctional reagents and antibody-drug conjugates - in addition to their dithiols' potential as high-performance reducing agents.

The Thiol Group Reactivity and the Antioxidant Property of Human Serum Albumin Are Controlled by the Joint Action of Fatty Acids and Glucose Binding.

The binding of ubiquitous serum ligands (free fatty acids) to human serum albumin (HSA) or its glycation can affect thiol group reactivity, thus influencing its antioxidant activity. The effects of stearic acid (SA) and glucose binding on HSA structural changes and thiol group content and reactivity were monitored by fluoroscopy and the Ellman method during a 14-day incubation in molar ratios to HSA that mimic pathophysiological conditions. Upon incubation with 5 mM glucose, HSA glycation was the same as HSA without it, in three different HSA:SA molar ratios (HSA:SA-1:1-2-4). The protective effect of SA on the antioxidant property of HSA under different glucose regimes (5-10-20 mM) was significantly affected by molar ratios of HSA:SA. Thiol reactivity was fully restored with 5-20 mM glucose at a 1:1 HSA:SA ratio, while the highest thiol content recovery was in pathological glucose regimes at a 1:1 HSA:SA ratio. The SA affinity for HSA increased significantly (1.5- and 1.3-fold, p < 0.01) with 5 and 10 mM glucose compared to the control. These results deepen the knowledge about the possible regulation of the antioxidant role of HSA in diabetes and other pathophysiological conditions and enable the design of future HSA-drug studies which, in turn, is important for clinicians when designing information-based treatments.

Optimization of hybrid gelatin-polysaccharide bioinks exploiting thiol-norbornene chemistry using a reducing additive.

Thiol-norbornene chemistry offers great potential in the field of hydrogel development, given its step growth crosslinking mechanism. However, limitations exist with regard to deposition-based bioprinting of thiol-containing hydrogels, associated with premature crosslinking of thiolated (bio)polymers resulting from disulfide formation in the presence of oxygen. More specifically, disulfide formation can result in an increase in viscosity thereby impeding the printing process. In the present work, hydrogels constituting norbornene-modified dextran (DexNB) combined with thiolated gelatin (GelSH) are selected as case study to explore the potential of incorporating the reducing agent tris(2-carboxyethyl)phosphine (TCEP), to prevent the formation of disulfides. We observed that, in addition to preventing disulfide formation, TCEP also contributed to premature, spontaneous thiol-norbornene crosslinking without the use of UV light as evidenced via1H-NMR spectroscopy. Herein, an optimal concentration of 25 mol% TCEP with respect to the amount of thiols was found, thereby limiting auto-gelation by both minimizing disulfide formation and spontaneous thiol-norbornene reaction. This concentration results in a constant viscosity during at least 24 h, a more homogeneous network being formed as evidenced using atomic force microscopy while retaining bioink biocompatibility as evidenced by a cell viability of human foreskin fibroblasts exceeding 70% according to ISO 10993-6:2016.

Silicon-Containing Thiol-Specific Bioconjugating Reagent.

A new bioconjugation reagent containing silicon has been developed for the selective reaction with thiols. The inclusion of silicon significantly improves chemoselectivity and suppresses retro processes, thereby exceeding the capabilities of traditional reagents. The method is versatile and compatible with a broad range of thiols and unsaturated carbonyl compounds and yields moderate to high results. These reactions can be conducted under biocompatible conditions, thereby making them suitable for protein bioconjugation. The resulting conjugates display good stability in the presence of various biomolecules, which suggests their potential application for the synthesis of antibody-drug conjugates. Furthermore, the presence of a silicon moiety within the conjugated products opens up new avenues for drug release and bridging inorganics with other disciplines. This new class of silicon-containing thiol-specific bioconjugation reagents has significant implications for researchers working in bioanalytical science and medicinal chemistry and leads to innovative opportunities for advancing the field of bioconjugation research and medicinal chemistry.

AChE activity self-breathing control mechanisms regulated by H2Sn and GSH: Persulfidation and glutathionylation on sulfhydryl after disulfide bonds cleavage.

Hydrogen sulfide (H2S), or dihydrogen sulfane (H2Sn), acts as a signal molecule through the beneficial mechanism of persulfidation, known as the post-translational transformation of cysteine residues to persulfides. We previously reported that Glutathione (GSH) could regulate enzyme activity through S-desulfurization or glutathionylation of residues to generate protein-SG or protein-SSG, releasing H2S. However, little is known about the mechanisms by which H2Sn and GSH affect the disulfide bonds. In this study, we provide direct evidences that H2Sn and GSH modify the sulfhydryl group on Cys272, which forms disulfide bonds in acetylcholinesterase (AChE), to generate Cys-SSH and Cys-SSG, respectively. Glutathionylation of disulfide is a two-step reaction based on nucleophilic substitution, in which the first CS bond is broken, then the SS bond is broken to release H2S. H2Sn and GSH controlled self-breathing motion in enzyme catalysis by disconnecting specific disulfide bonds and modifying cysteine residues, thereby regulating AChE activity. Here, we elucidated H2Sn and GSH mechanisms on disulfide in the AChE system and proposed a self-breathing control theory induced by H2Sn and GSH. These theoretical findings shed light on the biological functions of H2Sn and GSH on sulfhydryl and disulfide bonds and enrich the theory of enzyme activity regulation.

A label-free and washing-free method to detect biological thiols on a personal glucose meter utilizing glucose oxidase-mimicking activity of gold nanoparticles.

We herein developed a label-free and washing-free method to detect biological thiols (biothiols) on a personal glucose meter (PGM) utilizing the intrinsic glucose oxidase (GOx)-mimicking activity of gold nanoparticles (AuNPs). By focusing on the fact that this activity could be diminished by target biothiols through their binding onto the AuNP surface, we correlated the concentration of biothiols with that of glucose readily measurable on a PGM and successfully determined cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) down to 0.116, 0.059, and 0.133 µM, respectively, with high specificity against non-target biomolecules. We further demonstrated its practical applicability by reliably detecting target biothiol in heterogeneous human serum. Due to the meritorious features of PGM such as simplicity, portability, and cost-effectiveness, we believe that this work could serve as a powerful platform for biothiol detection in point-of-care settings.

Two red/blue-emitting fluorescent probes for quick, portable, and selective detection of thiophenol in food, soil and plant samples, and their applications in bioimaging.

Thiophenol (PhSH), which is widely used in many industries, poses significant health risks owing to its acute toxicity and irritating effects. Thus, the detection of PhSH is crucial for ensuring environmental and food safety. There is significant room for improvement in the sensing properties of the reported analytical methods, such as response time, detection limit, selectivity, and portable detection. Herein, we present two new red/blue fluorescence-emissive sensors (NS1 and NS2) for PhSH detection. After reacting with PhSH, NS1 exhibited a low detection limit (66.7 nM), red emission, fast response time of just 10 s, and large Stokes shift (240 nm). NS2 could detect PhSH with a low detection limit (75.8 nM), fast response time of 20 s, and blue emission. The noticeable color response and portability of the two probes made them suitable for on-site detection of PhSH in various samples, such as water, soil, plant, food samples, and living cells. Moreover, it has been shown that these probes could be used to determine PhSH content in smartphone applications, thin layer chromatography kits, and polysulfone capsule kits. Prepared probes have low cytotoxicity and show good permeability in tested living cells, which is important for early diagnosis, disease research, and emergency analysis. Compared with other studies, the proposed approach has remarkable advantages in terms of detection limit, portability, response time, and low cytotoxicity. Thus, it meets the crucial demand for ensuring health, environmental and food safety, and adherence to regulatory standards.

Identification of Serine-Containing Microcystins by UHPLC-MS/MS Using Thiol and Sulfoxide Derivatizations and Detection of Novel Neutral Losses.

Microcystins (MCs) are hepatotoxic cyclic heptapeptides produced by cyanobacteria, and their structural diversity has led to the discovery of more than 300 congeners to date. However, with known amino acid combinations, many more MC congeners are theoretically possible, suggesting many remain unidentified. Herein, two novel serine (Ser)-containing MCs were putatively identified in a Lake Erie cyanobacterial harmful algal bloom (cyanoHAB), using high-resolution UHPLC-MS as well as thiol and sulfoxide derivatization procedures. These MCs contain an α,ß-unsaturated carbonyl on methyl dehydroalanine (Mdha) residue that undergoes Michael addition to produce a thiol-derivatized MC. Derivatization reactions using various thiolation reagents were followed by MS/MS, and two Python codes were used for data analysis and structural elucidation of MCs. Two novel MCs containing Ser at position 1 (i.e., next to Mdha) were putatively identified as [Ser1]MC-RR and [Ser1]MC-YR. Using thiol- and sulfoxide-modified [Ser1]MCs, identifications were confirmed by the observation of specific neutral losses of the oxidized thiols or sulfoxides in CID-MS/MS spectra in both positive and negative electrospray ionization (ESI) modes. These novel neutral losses are unique for MCs with Mdha and an adjacent Ser residue. Data suggest that a gas-phase reaction occurs between oxygen from adjacent Ser residue and sulfur of the Mdha-bonded thiol or sulfoxide, which leads to the formation and detection of stable cyclic MC ions in MS/MS spectra at m/z values corresponding to the loss of oxidized thiols or oxidized sulfoxides from Ser1-containing MCs.

Mechanism of methylmercury photodegradation in the yellow sea and East China Sea: Dominant pathways, and role of sunlight spectrum and dissolved organic matter.

Mercury (Hg) is among the most concerned contaminants in the world due to its high toxicity, prevalent existence in the environments, and bioaccumulation via food chain. Methylmercury (MeHg) is the major form of Hg that accumulates along the food chain and poses threat to humans and wild life. Photodegradation is the dominant process that MeHg is eliminated from freshwater system and upper ocean. The formation of MeHg-dissolved organic matter (DOM) complexes and a variety of free radicals (FR)/reactive oxygen species (ROS) have been previously proposed to be involved in MeHg photodegradation. However, most of these studies were conducted in freshwater, and the mechanism of MeHg photodegradation in seawater remains unclear. In this study, the main pathways of MeHg photodegradation in the seawater of Yellow Sea (YS) and East China Sea (ECS) were investigated using FR/ ROS scavenger addition and DOM competing-ligand addition techniques. The results showed that direct photodegradation of MeHg-DOM complexes is the major pathway of MeHg photodegradation in the YS and ECS, while indirect photolysis of MeHg by hydroxyl radical (·OH) also plays a certain role at some sites. MeHg photodegradation was found to be mainly induced by ultraviolet (UV) light rather than visible light in YS and ECS seawater, and the contribution of UV-B was higher than UV-A which was opposite to that previously reported in freshwater. The energy for breaking the bond of CHg in MeHg-Cl complexes formed in seawater is higher than that in MeHg-DOM complexes and this may cause the relatively greater contribution of UV-B with higher energy to MeHg photodegradation in seawater. In addition, MeHg photodegradation in various fractions of natural DOM with different molecular weights, hydrophilicity/hydrophobicity and acid-base was tested. MeHg photodegradation rates (kd) varied in these fractions and kd in high molecular weight DOM and hydrophobic Acid (HOA) fractions were faster than that in the other fractions. A significantly positive correlation was observed between kd and thiol concentrations while there was no significant correlation between kd and other measured parameters representing the composition of DOM (specific UV absorbance at 254 nm (SUVA254), spectral slope (SR), chromophoric dissolved organic matter (CDOM), humification index (HIX), biological index (BIX) and fluorescent components). These results indicate that thiol may be the key functional group in DOM affecting the photodegradation of MeHg in the YS and ECS.

Exploring film forming ability and improving its bioadhesiveness by thiolation of mucilaginous polysaccharides from Cassia uniflora seeds for drug delivery application.

The objectives of the present work were to explore film forming ability of mucilaginous polysaccharides obtained from Cassia uniflora seeds and improving its bioadhesive potential by thiolation for drug delivery and other applications. Thiolation was achieved by esterification reaction with thioglycolic acid. The modification was confirmed by performing and comparing its zeta potential, DSC, and spectrophotometric characterization by FTIR and NMR with unmodified mucilaginous polysaccharide. The modified mucilaginous polysaccharides FTIR spectra showed an additional absorption band at 2565 cm-1 and new shifts appeared in the 1H (δ 3.24 and at δ 3.44 ppm) and 13C NMR spectra's (21.56 ppm) confirming the esterification of mucilaginous polysaccharides. The prepared films of thiolated and unmodified mucilaginous polysaccharides were evaluated for various parameters like thickness, pH, and weight measurement, The film formulation had a thickness of 0.16 to 0.18 mm, pH in the range of 6.79 to 7.09 and weight uniformity 0.89 to 0.94 mg. The results reveal that the films based on thiolated material improved bioadhesive properties after thiolation. The SEM photographs revealed a smooth surface of film formulations. The diclofenac-loaded film of thiolated mucilaginous polysaccharide also showed >1.5-fold an increase in in-vitro drug release and exhibited non Fickian transport mechanism. These findings could increase the possible applications of chemically modified-thiolated mucilaginous polysaccharides of Cassia uniflora seeds in drug delivery.

A low-shrinkage-stress and anti-bacterial adherent dental resin composite: physicochemical properties and biocompatibility.

Polymerisation shrinkage and biofilm accumulation are the two main problems associated with dental resin composites (DRCs) that induce secondary caries, which can cause restoration failure. Polymerisation shrinkage can lead to microleakage gaps between the tooth and the DRCs, causing the aggregation of bacteria and development of secondary caries. Reducing the shrinkage stress (SS) and improving the resistance to bacterial adhesion have always been the focus of this field in modifying DRCs. A thiol-ene resin system can effectively reduce the polymerisation SS via its step-growth mechanism for delaying the gel point. Fluorinated compounds can reduce the surface free energies, thereby reducing bacterial adhesion. Thus, in this study, a range of mass fractions (0, 10, 20, 30, and 40 wt%) of a fluorinated thiol-ene resin system were added to a fluorinated dimethacrylate resin system/tricyclo decanedimethanol diacrylate to create a fluorinated methacrylate-thiol-ene ternary resin matrix. DRCs were prepared using the obtained ternary resin matrix, and their physical and chemical properties, effect on bacterial adhesion, and biocompatibility were investigated. The results demonstrated that the volumetric shrinkage and SS of the DRCs were reduced with no reduction in conversion degree even after the thiol-ene resin system was added. All DRC-based fluorinated resin systems exhibited an excellent anti-bacterial adhesion effect, as evidenced by the colony-forming unit counts, live/dead bacterial staining, and crystal violet staining tests against Streptococcus mutans (S. mutans). The genetic expressions associated with the bacterial adhesion of S. mutans were substantially affected after being cultured with fluorinated DRCs. All fluorinated DRCs demonstrated good biocompatibility through the in vitro cytotoxicity test and live/dead staining images of the L-929 cells. The above results illustrate that the DRCs based on the fluorinated methacrylate-thiol-ene resin matrix can be potentially applied in clinical practice due to their low SS and anti-bacterial adhesion effect.

A Versatile Platform to Generate Shell-Cross-Linked Uniform Π-Conjugated Nanofibers with Controllable Length, High Morphological Stability, and Facile Surface Tailorability.

Living crystallization-driven self-assembly (CDSA) has emerged as an efficient route to generate π-conjugated-polymer-based nanofibers (CPNFs) with promising applications from photocatalysis to biomedicine. However, the lack of efficient tools to endow CPNFs with morphological stability and surface tailorability becomes a frustrating hindrance for expanding application spectrum of CPNFs. Herein, a facile strategy to fabricate length-controllable OPV-based (OPV = oligo(p-phenylenevinylene)) CPNFs containing a cross-linked shell with high morphological stability and facile surface tailorability through the combination of living CDSA and thiol-ene chemistry by using OPV5 -b-PNAAM32 (PNAAM = poly(N-allyl acrylamide)) as a model is reported. Uniform fiber-like micelles with tunable length can be generated by self-seeding of living CDSA. By taking advantage of radical thiol-ene reaction between vinyls of PNAAM corona and four-arm thiols, the shell of micelles can be cross-linked with negligible destruction of structure of vinylene-containing OPV core. The resulting micelles show high morphological stability in NaCl solution and PBS buffer, even upon heating at 80 °C. The introduced extra thiol groups in the cross-linked shell can be further employed to install extra functional moieties via convenient thiol-Michael-type reaction. Given the negligible cytotoxicity of resulting CPNFs, this strategy opens an avenue to fabricate various CPNFs of diverse functionalities for biomedicine.

Chemical Stability of Thiol and Flavanol Sulfonation Products during Wine Aging Conditions.

Bisulfite (HSO3-) is the predominant form of sulfur dioxide, present as free and bound to wine relevant electrophiles under wine acidic pH. While sulfonation reactions of flavanols and thiols have been recently reported as key for wine preservation against oxidation, the transient mechanisms and physicochemical parameters responsible for that remain unknown. In the present study, sulfonation reaction kinetics of thiols and flavanols were monitored under simulated wine aging conditions. The reaction products were then characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and their chemical stability during time was determined by 1H NMR spectroscopy. Thiol and flavanol sulfonation reaction yields were both promoted by the presence of iron and oxygen, while their chemical stability was confirmed under the same conditions. The sulfonation derivatives of epicatechin and cysteine were synthesized and quantified in young and aged wines. Higher concentrations were reported for both metabolites in older wines, indicating their participation on the strongly bound sulfur dioxide fraction. These findings offer new prospects for more precise use of sulfur dioxide in winemaking.